Search

Background: Itraconazole is a potent inhibitor of CYP3A4 and P-glycoprotein, but not CYP2C9. Herein, we report a case study in which the plasma concentration of the CYP2C9 substrate (S)-warfarin, and not the CYP3A4 substrate (R)-warfarin, increased with itraconazole coadministration., Case: A 67-y-old man received an allogenic bone marrow transplant for acute lymphoid leukemia. He was taking oral itraconazole (200mg/day) and was started on a warfarin dose of 2.0mg/day. The plasma concentrations of (S)- and (R)-warfarin 3 days after starting warfarin administration were 216 and 556 ng/mL, respectively (INR 0.98), and after 10 days, the concentrations were 763 and 545 ng/mL, respectively (INR 2.43). On day 11 after withdrawal of itraconazole, the concentrations of (S)- and (R)-warfarin were 341 and 605ng/mL, respectively (INR 1.38). The concentration of (R)-warfarin was not affected by itraconazole; however, the final (S)-warfarin concentration had increased 7.3-fold. The (S)-warfarin/(S)-7-hydroxywarfarin ratio decreased to 2.45 from 8.40 after discontinuation of itraconazole. The permeability of warfarin enantiomers across Caco-2 cells was not influenced by itraconazole and showed no difference between enantiomers., Conclusions: Careful INR monitoring is necessary for warfarin co-administration with itraconazole. Further examination is necessary to elucidate mechanisms of the interaction between warfarin and itraconazole., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Lipoprotein lipase (LPL) mass is present in pre-heparin serum, although its activity is rarely detected. To clarify the dynamics of pre-heparin LPL mass during pregnancy, we studied the relationship between pre-heparin LPL mass and lipids in normal pregnant women., Methods: Pre-heparin LPL mass and serum lipid levels were measured in 99 pregnant women during all three trimesters., Results: When compared with the first and second trimesters, a significant decrease in pre-heparin LPL mass was observed in the third trimester. Plasma triglycerides were negatively correlated with pre-heparin LPL mass (r=-0.30; p<0.05). In contrast, LDL-C, HDL-C and total cholesterol did not exhibit a statistically significant correlation., Conclusion: The decrease in pre-heparin LPL mass is manifested only during the third trimester.

Background: Coronary heart disease (CHD) prevalence appears low among Japanese. Analysis of their negative risk factors is therefore important for public health strategy., Methods: We analyzed the impact on coronary atherosclerosis of sex, alcohol intake, plasma lipoproteins and enzymes to regulate cholesterol transport, lipoprotein lipase (LPL) and lecithin:cholesterol acyltransferase (LCAT) for the 110 patients who underwent coronary angiography, consecutively enrolled by excluding those >70 years or under hypolipidemic-drug treatment. Subgroup combinations compared were males vs. females in non-drinkers, and drinkers vs. non-drinkers in males., Results: Coronary stenosis was less in females and in drinkers, accompanied by high-density lipoprotein (HDL) in the respective comparison. LPL associated with sex (females>males) and LCAT with alcohol intake (drinkers>non-drinkers) although neither enzyme demonstrated direct correlation with coronary stenosis. LPL positively associated only with HDL in most of subgroups and LCAT correlated with low-density lipoprotein (LDL) in all subgroups but with HDL only in males., Conclusions: Among non-drinkers, females are at lower risk for coronary atherosclerosis than males mainly due to higher HDL in potential association with high LPL, and that drinkers are protected among males also by high HDL that is in apparent association with LCAT.

We expressed the extracellular domain (20-408 aa, (T) of human TSH receptor (TSHR) in E. coli to detect TSHR autoantibodies (TRAb) and, moreover, we expressed the two portions (20-218 aa (5') and 217-408 aa (3')) of the extracellular domain thought to distinguish thyroid stimulating antibodies (TSAb) from blocking antibodies (TSBAb), using pGEX.3X as the expression vector. Using Western blotting analysis of the sera from patients with autoimmune thyroid disease, sera from Graves' patients and patients with idiopathic myxedema who had TSBAb reacted with the fusion protein (T), but none of the control sera reacted with it. We further evaluated whether or not the positive sear for T recognized fusion proteins (5') or (3'). The sera from Graves' patients reacted with both fusion proteins (5') and (3'). The sera from patients with idiopathic myxedema did not react with either of fusion proteins (5') or (3'). These findings suggest that these recombinant TSHR proteins could be used as antigens to detect TRAb, and differentiate TSABb from patients with idiopathic myxedema.

We measured the anti-skeletal muscle (SM) antibody titers in sera from 46 patients with thymoma but without Myasthenia gravis (MG) in order to determine whether the presence of anti-SM antibody is linked to the combination of thymoma-MG, or to thymoma alone. We detected anti-SM antibodies in 18 of these sera, of which 15 had concomitantly elevated titers of anti-AChR antibodies. Moreover, 9 of whom had experienced the onset of MG after surgery. In contrast, no patient without elevations in both antibodies developed MG during the followup. We conclude that the presence of anti-SM antibodies is linked strongly with thymoma associated with MG, but not with thymoma alone.

A two-site enzyme immunoassay for slow moving protease (SMP) of human gastric mucosa has been developed. The detection limit of SMP was 50 pg/tube and the optimal assay range was 0.5 to 50 ng/tube. This assay system made it possible to measure a trace amount of gastric mucosal SMP in endoscopic biopsy-specimens. Mean gastric mucosal SMP contents of the antrum, the angles, and the distal and proximal corpuses were 4.5, 3.7, 2.6, and 2.5 micrograms/mg protein, respectively. The antral mucosa contained a larger amount of SMP than the gastric mucosa of other area. The present enzyme immunoassay system is sufficiently sensitive for the clinical study of SMP in gastrointestinal tract.

A new two-site enzyme immunoassay for pepsinogen II(PGII) has been developed. The detection limit of PGII was 0.15 ng/ml (15 pg/tube) and the optimal assay range was 1.5 to 150 ng/ml (150 pg to 15 ng/tube). Mean serum PGII concentrations in normal males and females were 17.2 and 14.6 ng/ml, respectively. The chronological analysis among 5 age groups from 20 to 69 yr, males and females together, revealed that the serum level was low (11.9 ng/ml) between 20-39 yr, gradually increased from 40 yr of age and attained the maximum (22.5 ng/ml) in the 50-yr group. Total gastrectomy markedly lowered the serum level to 1.9 ng/ml, suggesting that the majority of PGII in serum was derived from the gastric mucosa. This assay makes it possible to measure trace amounts of PGII derived from extragastric as well as gastroduodenal tissues.

A sandwich enzyme immunoassay for epidermal growth factor (EGF) has been developed which measures EGF concentrations in serum, urine, saliva, gastric and pancreatic juices without pretreatment. Sensitivity for human EGF is 500 fg/tube. Serum EGF concentration in normal males and females is 780 and 604 pg/ml, respectively. Urinary human EGF is 51.3 ng/mg creatinine for males, and 68.3 ng/mg creatinine for females. The difference is not significant, and no correlation between serum and urinary concentrations exists, but serum concentration changes with age. The highest concentration is seen up to 9 years of age, suggesting that EGF promotes cell proliferation during growth.